A novel pituitary tumor transforming gene identified

Over the next few days I'll take a look at several recent articles about pituitary tumors. This first post highlights The molecular biology of pituitary tumors: a personal perspective by Ashley B. Grossman, renowned Professor of Neuroendocrinology at St. Bartholomew's in the UK. Prof. Grossman draws on his extensive experience with pituitary tumors to highlight what is known about them and what needs to be further explored.

Efforts to establish the ‘cause’ of pituitary tumors have, therefore, focussed on three main areas:

• The mutations involved in genetic syndromes associated with pituitary tumors have been identified and assessed in sporadic adenoma;
• Abnormalities in pituitary-specific signaling pathways have been studied;
• Any candidate genes that could potentially be involved have been studied in animal models of pituitary tumor formation.

In this short report, the findings of this research are summarised, using some of our own studies to look for a commonality of theme.

The behavior of pituitary tumors is notable because they offer information about more aggressive tumors. Genetic studies have offered a lot of information about Carney's Complex, MEN1, and isolated familial somatotropinomas (IFS) but have failed to give much information about "sporadic" pituitary tumors.

Although "abnormalities in the signaling and feedback pathways have been demonstrated in pituitary tumors" causing Cushing's Disease and acromegaly, the evidence currently available does not show they are the cause of the tumors. Conversely, these are probably acquired due to the disease.

There are, however, some pathways which are interesting. According to the article:

• There is abundant evidence that many cell cycle inhibitors involved in the normal regulation of the cell cycle are under-expressed in sporadic adenomas,including p16, p18 and p27 [23], and such dysregulation can be shown to cause chromosomal destabilisation...

  Other cell cycle inhibitors are also under-expressed in pituitary adenomas, but in many cases these are at the level of transcriptional control...

  A novel gene transcript PTTG has been identified in rat GH4 pituitary tumors, and this has been shown to be overexpressed in a large proportion of pituitary tumors compared to the normal pituitary [34]. Furthermore, expression appears to be correlated with invasiveness...

  Despite much excellent research into pituitary adenomas, all that can be stated for sure is that secretory tumors have defective feedback, pituitary tumors are characterised by over-activity of both the Akt pathway and the MAPK pathway, and we can speculate that this may relate in some way to aberrant methylation of tumor suppressor gene promoters.

Professor Grossman concludes:

Little information can be gained from the data presented here to explain the pathogenesis of more aggressive pituitary tumors, since these generally exhibit the same changes described here but to an exaggerated degree. The potential role of PTTG in tumorigenesis and invasiveness has yet to be determined but this gene could play an important role in aggressive tumors.

This is just a brief synopsis of the whole article with much of the technical detail weeded out for ease of understanding by the general reader. However, it outlines some interesting research with reference to the same.

Ashley B. Grossman (2008). The molecular biology of pituitary tumors: a personal perspective Pituitary DOI: 10.1007/s11102-008-0158-7